Keratin treatment formulations and methods

ABSTRACT

Formulations, kits, and methods for rebuilding the disulfide bonds in keratin found in hair, skin, or nails. Hair that is damaged due to a hair coloring treatment and/or other reducing treatment, such as during a permanent wave, can be treated with the formulations containing one or more active agents. The formulations may be applied subsequent to a hair coloring treatment or simultaneously with a hair coloring treatment. Use of the active agent formulations during a permanent wave treatment prevents the reversion of the hair to its previous state, for at least one week, preferably at least three months, more preferably at least one year, most preferably greater than one year, after one or more than one application of the formulation. Application of the active agent formulation to skin or nails can help repair damaged disulfide bonds due to natural wear and tear or natural aging.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application Ser.No. 61/994,709, filed May 16, 2014, the disclosure of which isincorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The present invention generally relates to formulations and methods fortreating keratin in hair, skin, or nails, and in particular forstrengthening and/or repairing hair during or after a coloring orpermanent wave treatment.

BACKGROUND OF THE INVENTION

Hair coloring is currently a globally accepted fashion phenomenon. Colortreatments include hair coloring, highlighting, and bleaching. Thecoloring products can be categorized in several types, which includepermanent, demi-permanent, semi-permanent, and temporary coloringformulations. Permanent hair coloring products make up the majority ofthe market worldwide.

Significant effort has been directed towards developing variousapproaches to hair dyeing; these include, oxidative dyes, direct actiondyes, natural dyes, metallic dyes and reactive dyes. Many hair coloringformulations, in particular permanent coloring formulations, usereducing agents to break the disulfide bonds in the hair allowing deeperpenetration of the hair coloring dyes and bleaching agents into thehair.

Disulfide bond linkages in hair are also broken by application ofreducing agents, such as during permanent wave and hair straighteningprocess. After the disulfide bonds are broken, the hair is placed instress to establish the final style (e.g., straight, wavy, or curly),and the disulfide bonds are re-established.

Thioglycolic acid, particularly as the ammonium salt, is often used tocleave the cysteine disulfide bonds present in hair. Sodium bisulfite isanother example of a known reducing agent commonly used in various dyesand bleaching agents in color treatments.

Typically, oxidation to restore the reduced bond is partially obtainedwhen an oxidizing agent, such as hydrogen peroxide is present in acoloring formulation and/or by exposing the hair to atmospheric oxygen.However, this oxidation step can be very slow and can leave the hairfrizzy and damaged.

Similarly, hair undergoing a permanent wave treatment is typicallytreated with a reducing agent followed by an oxidizing agent. Hydrogenperoxide is optionally added in a second step to restore the hair to itsprior state. The newly formed disulfide bonds of the treated hair areunder stress to maintain the hair's new shape; thus, they break easilyresulting in a reversion of the hair style over time.

The use of peroxides in the hair styling process can result in damagedhair, removal of non-natural color from the hair, and/or leave the hairfrizzy. Furthermore, some latent reduced thiols may remain in the haireven after oxidative treatment. Hair styling treatments with peroxidesinvolve the following reaction with thiol groups:

2K-S—H+H₂O₂ →K-S—S-K2 H₂O   (Reaction I)

where K represents keratin in the hair.

In the case where two K-S—H groups are not present for Reaction I totake place, it is believed that the following reaction takes place,which results in damaged hair:

K-S—H+H₂O₂ →K-SO₂—OH   (Reaction II).

In addition to being a major component in hair, keratin is also a majorcomponent in skin and nails. There are a number of different types ofkeratin and they are generally grouped as soft or hard keratins. Softkeratins are more prevalent in skin, while hard keratins predominate inhair and nails. Nails, in particular, are made of a modified keratinsimilar to that found hair. The disulfide bonds of the keratin in nailscontribute to their impermeability. Therefore, damage to the disulfidebridges of keratin present in skin or nails can result in unhealthyand/or flaky skin or nails. Maintaining the disulfide bridges of keratintherefore helps to keep skin healthy and prevents cracking and splittingin nails.

Substantial improvement is needed in the areas of color saturation,color development, precise initial color consistency, improved washfastness, and improved hair conditioning when applying color treatments.For example, the attainment of precise initial colors that are retainedby the hair for a desirable time period has remained an elusive goal.The coloring formulations also cause severe hair damage, especially whencoloring treatments are repeated. Moreover, various standard dailyactions to the hair, for example hair brushing, hair blow-drying, andsun light exposure can cause even more damage to the hair.

Similar damage to the hair can also result from permanent wavetreatments. In both coloring and permanent wave processes, improvementsare also needed to repair damage and/or to strengthen the hair during orafter such styling treatments. Additionally, improved treatments andmethods are needed which can be applied to skin and nails to repairdamaged keratin.

There is a need for hair formulations and treatments that repair and/orstrengthen keratin in hair damaged from coloring and/or permanent wavetreatments using reducing treatments.

There is also a need for hair formulations and treatments that canrepair latent reduced thiols present in hair.

There is also a need for formulations and treatments that can repairdamage to keratin present in skin and hair.

Therefore, it is an object of this invention to provide improvedformulations and methods for repairing and/or strengthening damagedhair.

It is also an object of this invention to provide methods for usingformulations that repair and/or strengthen hair after and/or duringcoloring or permanent wavetreatments.

It is also an object of this invention to provide formulations andmethods for using these formulations to repair and/or strengthen hairafter a reducing treatment.

It is also an object of this invention to provide formulations andmethods for using these formulations that repair and/or strengthenkeratin in hair, skin or nails due to natural wear and tear or due tonatural aging.

SUMMARY OF THE INVENTION

Formulations, kits, and methods for restoring hair that has been brokenduring a hair coloring or permanent wave treatment are disclosed. Theformulations have similar benefits when used with different colorchemical processes, such as bleaching, highlights, lowlights,semi-permanent, demi-permanent, and permanent color. Improved methods ofstyling hair, for example permanent hair waving and hair curling arealso provided. The formulations can be applied each time the hair iswashed or daily, once-weekly, twice-weekly, biweekly, once-monthly,every other month, or at less frequent intervals. Preferably, theformulations are applied once-monthly to achieve the desired results.

Traditional methods of permanent hair waving, hair curling, orstraightening use hydrogen peroxide after a reducing treatment. Theprocess generally takes about three days to complete. The methodsdisclosed herein use active agents to repair the hair; these activeagents are washed from the individual's hair on the same day that theyare applied to the hair. Under the same conditions, such as temperatureand moisture, hair treated with the formulations disclosed herein takesa longer time to revert to its prior state as compared to the same hairthat is treated with hydrogen peroxide.

The formulations disclosed herein contain one or more polyfunctionalcompounds. The polyfunctional compound contains at least one ionizablefunctional group capable of forming ionic bonds, and the polyfunctionalcompound also contains at least one functional group capable of forminga covalent bond with a thiol group. In some embodiments, thepolyfunctional compounds contains at least two ionizable groups.Optionally, the formulation is applied at the same time as the haircoloring or permanent wave treatment. Alternatively, the formulation maybe applied after the hair coloring or permanent wave treatment or todamaged hair. For example, the formulations can be applied within oneweek of the hair being treated and/or damaged, preferably within threedays, more preferably within two days, most preferably immediately afterapplication of the coloring or permanent wave treatment.

DETAILED DESCRIPTION OF THE INVENTION I. Definitions

The term “hair” refers to one or more than one strand of hair, as wellas the natural components of hair, such as oil from a body. Hair alsorefers to virgin hair or processed hair, for example hair that has beenexposed to hair waving or hair straightening formulations.

“Pharmaceutically acceptable” and “cosmetically acceptable” are usedinterchangeably and refer to those compounds, materials, and/orformulations, which are, within the scope of sound medical judgment,suitable for use in contact with the tissues of human beings and animalswithout excessive toxicity, irritation, allergic response, or otherproblems or complications commensurate with a reasonable benefit/riskratio. More specifically, pharmaceutically acceptable refers to amaterial, compound, or formulation that is suitable for use in contactwith the skin, scalp, or hair. Pharmaceutically acceptable materials areknown to those of ordinary skill in the art.

“Shampoo”, as used herein, generally refers to a liquid or semi-solidformulation applied to hair that contains detergent or soap for washingthe hair.

“Conditioner”, as used herein, generally refers to a formulation (e.g.,liquid, cream, lotion, gel, semi-solid) applied to hair to soften thehair, smooth the hair, and/or change the sheen of the hair.

“Analog” and “derivative” are used herein interchangeably, and refer toa compound that possesses the same core as the parent compound, butdiffers from the parent compound in bond order, the absence or presenceof one or more atoms and/or groups of atoms, or a combination thereof.The derivative can differ from the parent compound, for example, in oneor more substituents present on the core, which may include one or moreatoms, functional groups, or substructures. In general, a derivative canbe formed, at least theoretically, from the parent compound via chemicaland/or physical processes.

“Electrophilic group” or “electrophilic moiety” are used interchangeablyand refer to one or more functional groups or moieties that have anaffinity for or attract electrons.

“Nucleophilic group” or “nucleophilic moiety” are used interchangeablyand refer to one or more functional groups or moieties that are electronrich and are capable of reacting with electrophilic groups.

“Michael acceptor”, as used herein, is a species of electrophilic groupsor moieties that participates in nucleophilic addition reactions. TheMichael acceptor can be or can contain an α,β-unsaturatedcarbonyl-containing group or moiety, such as a ketone. Other Michaelacceptors include pi-bonds, such as double or triple bonds conjugated toother pi-bond containing electron withdrawing groups, such as nitrogroups, nitrile groups, and carboxylic acid groups.

“Carboxylic acid,” as used in here refers to the group —COOH. Unlessspecified otherwise the term carboxylic acid embraces both the free acidand carboxylate salt.

“Alkyl”, as used herein, refers to the radical of saturated orunsaturated aliphatic groups, including straight-chain alkyl, alkenyl,or alkynyl groups, branched-chain alkyl, alkenyl, or alkynyl groups,cycloalkyl, cycloalkenyl, or cycloalkynyl (alicyclic) groups, alkylsubstituted cycloalkyl, cycloalkenyl, or cycloalkynyl groups, andcycloalkyl substituted alkyl, alkenyl, or alkynyl groups. Unlessotherwise indicated, a straight chain or branched chain alkyl has 30 orfewer carbon atoms in its backbone (e.g., C₁-C₃₀ for straight chain,C₃-C₃₀ for branched chain), more preferably 20 or fewer carbon atoms,more preferably 12 or fewer carbon atoms, and most preferably 8 or fewercarbon atoms. In some embodiments, the chain has 1-6 carbons. Likewise,preferred cycloalkyls have from 3-10 carbon atoms in their ringstructure, and more preferably have 5, 6 or 7 carbons in the ringstructure. The ranges provided above are inclusive of all values betweenthe minimum value and the maximum value.

The term “alkyl” includes both “unsubstituted alkyls” and “substitutedalkyls”, the latter of which refers to alkyl moieties having one or moresubstituents replacing a hydrogen on one or more carbons of thehydrocarbon backbone. Such substituents include, but are not limited to,halogen, hydroxyl, carbonyl (such as a carboxyl, alkoxycarbonyl, formyl,or an acyl), thiocarbonyl (such as a thioester, a thioacetate, or athioformate), alkoxyl, phosphoryl, phosphate, phosphonate, aphosphinate, amino, amido, amidine, imine, cyano, nitro, azido,sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido,sulfonyl, heterocyclyl, aralkyl, or an aromatic or heteroaromaticmoiety.

Unless the number of carbons is otherwise specified, “lower alkyl” asused herein means an alkyl group, as defined above, but having from oneto ten carbons, more preferably from one to six carbon atoms, in itsbackbone structure. Likewise, “lower alkenyl” and “lower alkynyl” havesimilar chain lengths. Preferred alkyl groups are lower alkyls.

The alkyl groups may also contain one or more heteroatoms within thecarbon backbone. Examples include oxygen, nitrogen, sulfur, andcombinations thereof. In certain embodiments, the alkyl group containsbetween one and four heteroatoms.

“Alkenyl” and “Alkynyl”, as used herein, refer to unsaturated aliphaticgroups containing one or more double or triple bonds analogous in length(e.g., C₂-C₃₀) and possible substitution to the alkyl groups describedabove.

“Aryl”, as used herein, refers to 5-, 6- and 7-membered aromatic rings.The ring may be a carbocyclic, heterocyclic, fused carbocyclic, fusedheterocyclic, bicarbocyclic, or biheterocyclic ring system, optionallysubstituted as described above for alkyl. Broadly defined, “Ar”, as usedherein, includes 5-, 6- and 7-membered single-ring aromatic groups thatmay include from zero to four heteroatoms. Examples include, but are notlimited to, benzene, pyrrole, furan, thiophene, imidazole, oxazole,thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine andpyrimidine. Those aryl groups having heteroatoms in the ring structuremay also be referred to as “heteroaryl”, “aryl heterocycles”, or“heteroaromatics”. The aromatic ring can be substituted at one or morering positions with such substituents as described above, for example,halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl,alkoxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate,phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl,sulfonamido, ketone, aldehyde, ester, heterocyclyl, aromatic orheteroaromatic moieties, —CF₃, and —CN. The term “Ar” also includespolycyclic ring systems having two or more cyclic rings in which two ormore carbons are common to two adjoining rings (the rings are “fusedrings”) wherein at least one of the rings is aromatic, e.g., the othercyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, arylsand/or heterocycles, or both rings are aromatic.

“Alkylaryl”, as used herein, refers to an alkyl group substituted withan aryl group (e.g., an aromatic or hetero aromatic group).

“Heterocycle” or “heterocyclic”, as used herein, refers to a cyclicradical attached via a ring carbon or nitrogen of a monocyclic orbicyclic ring containing 3-10 ring atoms, and preferably from 5-6 ringatoms, containing carbon and one to four heteroatoms each selected fromnon-peroxide oxygen, sulfur, and N(Y) wherein Y is absent or is H, O,(C₁₋₄) alkyl, phenyl or benzyl, and optionally containing one or moredouble or triple bonds, and optionally substituted with one or moresubstituents. The term “heterocycle” also encompasses substituted andunsubstituted heteroaryl rings. Examples of heterocyclic ring include,but are not limited to, benzimidazolyl, benzofuranyl, benzothiofuranyl,benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl,benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl,benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl,chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl,imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl,indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl,isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl,isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl,naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl,oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl,phenazinyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, phthalazinyl,piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl,pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole,pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl,pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl,quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl,tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl,thienooxazolyl, thienoimidazolyl, thiophenyl and xanthenyl.

“Heteroaryl”, as used herein, refers to a monocyclic aromatic ringcontaining five or six ring atoms containing carbon and 1, 2, 3, or 4heteroatoms each selected from non-peroxide oxygen, sulfur, and N(Y)where Y is absent or is H, O, (C₁-C₈) alkyl, phenyl or benzyl.Non-limiting examples of heteroaryl groups include furyl, imidazolyl,triazolyl, triazinyl, oxazoyl, isoxazoyl, thiazolyl, isothiazoyl,pyrazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridyl, (or its N-oxide),thienyl, pyrimidinyl (or its N-oxide), indolyl, isoquinolyl (or itsN-oxide), quinolyl (or its N-oxide) and the like. The term “heteroaryl”can include radicals of an ortho-fused bicyclic heterocycle of abouteight to ten ring atoms derived therefrom, particularly abenz-derivative or one derived by fusing a propylene, trimethylene, ortetramethylene diradical thereto. Examples of heteroaryl include, butare not limited to, furyl, imidazolyl, triazolyl, triazinyl, oxazoyl,isoxazoyl, thiazolyl, isothiazoyl, pyraxolyl, pyrrolyl, pyrazinyl,tetrazolyl, pyridyl (or its N-oxide), thientyl, pyrimidinyl (or itsN-oxide), indolyl, isoquinolyl (or its N-oxide), quinolyl (or itsN-oxide), and the like.

“Halogen”, as used herein, refers to fluorine, chlorine, bromine, oriodine.

The term “substituted,” as used herein, refers to all permissiblesubstituents of the compounds described herein. In the broadest sense,the permissible substituents include acyclic and cyclic, branched andunbranched, carbocyclic and heterocyclic, aromatic and nonaromaticsubstituents of organic compounds. Illustrative substituents include,but are not limited to, halogens, hydroxyl groups, or any other organicgroupings containing any number of carbon atoms, preferably 1-14 carbonatoms, and optionally include one or more heteroatoms such as oxygen,sulfur, or nitrogen grouping in linear, branched, or cyclic structuralformats. Representative substituents include alkyl, substituted alkyl,alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl,substituted phenyl, aryl, substituted aryl, heteroaryl, substitutedheteroaryl, halo, hydroxyl, alkoxy, substituted alkoxy, phenoxy,substituted phenoxy, aroxy, substituted aroxy, alkylthio, substitutedalkylthio, phenylthio, substituted phenylthio, arylthio, substitutedarylthio, cyano, isocyano, substituted isocyano, carbonyl, substitutedcarbonyl, carboxyl, substituted carboxyl, amino, substituted amino,amido, substituted amido, sulfonyl, substituted sulfonyl, sulfonic acid,phosphoryl, substituted phosphoryl, phosphonyl, substituted phosphonyl,polyaryl, substituted polyaryl, C₃-C₂₀ cyclic, substituted C₃-C₂₀cyclic, heterocyclic, substituted heterocyclic, aminoacid, peptide, andpolypeptide groups.

Heteroatoms, such as nitrogen, may have hydrogen substituents and/or anypermissible substituents of organic compounds described herein thatsatisfy the valences of the heteroatoms. It is understood that“substitution” or “substituted” includes the implicit proviso that suchsubstitution is in accordance with permitted valence of the substitutedatom and the substituent, and that the substitution results in a stablecompound, i.e. a compound that does not spontaneously undergotransformation such as by rearrangement, cyclization, elimination, etc.

“Polymer”, as used herein, refers to a molecule containing more than 10monomer units.

“Water-soluble”, as used herein, generally means at least 50, 75, 100,125, 150, 200, 225, or 250 g is soluble in 1 L of water at 25° C.

II. Formulations

The formulations and methods disclosed herein are concerned withtreating keratin in hair, skin, or nails. In one embodiment, the methodsrelate to strengthening and/or repairing hair after it has undergone acoloring treatment or after or during a permanent wave treatment.Additionally, the formulations may reduce or prevent hair damage due tohair coloring and/or bleaching processes.

A. Formulations

The formulations contain one or more polyfunctional compounds (alsoreferred to herein as “active agents”).

The active agents can be combined with one or more pharmaceuticallyacceptable carriers and/or excipients that are considered safe andeffective to human hair and/or human scalp, and may be administered toan individual's hair without causing undesirable biological sideeffects, such as burning, itching, and/or redness, or similar adversereactions. The formulations may further contain an excipient thatrenders the formulations neutral pH, or a pH ranging from about pH 3 toabout pH 12, preferably from pH 5 to pH 8.

The active agent is typically present in an amount ranging from about0.01 wt % to about 50 wt % of the formulation, preferably from aboutfrom about 1 wt % to about 25 wt % of the formulation, more preferablyfrom about 1 wt % to about 15 wt %, most preferably from about 1 wt % toabout 10 wt %. Typically, the active agent may be present in an amountranging from about 0.5 to about 3 wt % of the formulation, or from about1 to about 3 wt % of the formulation.

The active agent is stable in aqueous solution for a period of at least2, 3, 4, 5, 6, 8, 9, 10, 11, or 12 months or longer at pH of 6 to 8 anda temperature of about 25-30° C., preferably about 25° C. “Stable” asused herein with respect to shelf-life means that at least 40, 45, 50,55, 60, 65, 70, 75, 80, 85, 90, or 95% of the compound is unchanged overthe specified period.

a. Active Agents

The active agent is a polyfunctional compound that may contain ionizablefunctional groups capable of forming ionic bonds and functional groupscapable of forming a covalent bond with a thiol. Suitable ionizablefunctional groups include, but are not limited to, acidic groups such ascarboxylic acids, sulfonic acids, phosphonic acids, and basic groups,such as amines. Suitable functional groups capable of forming a covalentbond with a thiol include, but are not limited to, Michael acceptors,alkyl halides or sulfonate esters.

The active agent may have the following Formula I:

(B)_(m)—Z-(A)_(n)   Formula I

wherein Z is a linker or is absent, m and n are each an integerindependently selected from 0-6, provided that m+n is at least 2, B is afunctional group capable of forming a covalent bond with a thiol, and Ais an ionizable functional group. In some embodiments, ionizable group Acan be independently selected from the group consisting of: —COOH,—SO₃H, —PO₃H₂, and —N(R¹)₂; wherein R¹ is independently selected fromthe group consisting of a hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,aryl, heterocycloalkyl and heteroaryl groups; wherein each R¹ isindependently unsubstituted or substituted with one or moresubstituents. In some other embodiments, ionizable group A can be anionic group, such as —N⁺(R¹)₃. In some preferred embodiments, each R¹ isindependently selected from a methyl, ethyl, or isopropyl group.

Exemplary active agents according to Formula I may contain thiolreactive functional groups, as group B, for example, such as those shownin the following moieties:

wherein R is independently selected from hydrogen, C₁₋₆ alkyl, aryl, oran ionizable functional group; Z′ is oxygen (O), NH, or is absent; and Gis carbon (C) and g is 1, or G is sulfur (S) and g is 2.

The linker Z, when present, can be or can contain an alkyl, alkenyl,cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl or heteroaryl group.One or more of the carbon atoms in the alkyl, alkenyl, cycloalkyl,cycloalkenyl, and aryl groups can be substituted with a heteroatom,yielding, for instance, an ether or alkylamine-containing linker.

The linker Z may optionally be substituted with one or moresubstituents, which may be the same or different, including hydrogen,halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl,heterocycloalkyl, heteroaryl, amine, hydroxy, oxo, formyl, acyl,carboxylic acid (—COOH), —C(O)R¹, —C(O)OR¹, carboxylate (—COO—), primaryamide (e.g., —CONH₂), secondary amide (e.g., —CONHR₁₁), —C(O)NR¹R²,—NR¹R², —NR¹S(O)₂R², —NR¹C(O)R², —S(O)₂R² , —SR¹, and —S(O)₂NR¹R²,sulfinyl group (e.g., —SOR₁), and sulfonyl group (e.g., —SOOR₁); whereinR¹ and R² may each independently be hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocycloalkyl and heteroaryl; wherein each of R¹and R² is optionally independently substituted with one or moresubstituents selected from the group consisting of halogen, hydroxyl,oxo, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionallysubstituted with one or more halogen or alkoxy or aryloxy, aryloptionally substituted with one or more halogen or alkoxy or alkyl ortrihaloalkyl, heterocycloalkyl optionally substituted with aryl orheteroaryl or oxo or alkyl optionally substituted with hydroxyl,cycloalkyl optionally substituted with hydroxyl, heteroaryl optionallysubstituted with one or more halogen or alkoxy or alkyl or trihaloalkyl,haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl and dialkylaminocarbonyl.

In certain preferred embodiments, the linker Z is a C₁₋₁₀ alkyl groupwhich may be unsubstituted or substituted one or more times by oxo,hydroxyl, carboxyl, amido or amino. Preferably, the linker Z is a C₁₋₄alkyl group. The alkyl group may be linear or branched. The alkyl groupmay also be interrupted one or more times by a heteroatom selected fromoxygen, sulfur and nitrogen. An example of such a di-carboxylic acidshaving a heteroatom interruption is thiodipropionic acid. In otherembodiments, the alkyl group may contain one or more double or triplebonds.

In some embodiments, the active agent of Formula I has one of thefollowing structures:

or is a simple salt of these structures.

In certain other embodiments, the active agent may have the followingFormula II:

(B)_(m)—Z-(A)_(n)-(C)_(o)   Formula II

wherein Z is a linker or is absent, m and n are each an integerindependently selected from 0-6, provided that m+n is at least 2, B is afunctional group capable of forming a covalent bond with a nucleophile,such as but not limited to a thiol or amine group, A is an ionizablefunctional group as defined above, and C contains an ionic group and afunctional group which is also capable of forming a covalent bond with anucleophile, such as but not limited to a thiol or amine group, andwhich has a charge opposite to that of ionizable group A. Group C isionically bonded (denoted by dashed line) to group A. For ionic group C,o is an integer value independently selected from 0-6, such that the sumof charges of group C and ionizable group A is zero. In someembodiments, ionizable group A can be independently selected from thegroup consisting of: —COOH, —SO₃H, —PO₃H₂, and —N(R¹)₂; wherein R¹ isindependently selected from the group consisting of a hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl and heteroarylgroups; wherein each R¹ is independently unsubstituted or substitutedwith one or more substituents. In some other embodiments, ionizablegroup A can be an ionic group such as —N⁺(R¹)₃. In some preferredembodiments, each R¹ is independently selected from a methyl, ethyl, orisopropyl group.

The active agents according to Formula II may contain thiol reactivefunctional groups as group B, for example, such as those shown in thefollowing moieties:

wherein R is independently selected from hydrogen, C₁₋₆ alkyl, aryl, oran ionizable functional group; Z′ is oxygen (O), NH, or is absent; and Gis carbon (C) and g is 1, or G is sulfur (S) and g is 2.

The linker Z, when present, can be or can contain an alkyl, alkenyl,cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl or heteroaryl group.One or more of the carbon atoms in the alkyl, alkenyl, cycloalkyl,cycloalkenyl, and aryl groups can be substituted with a heteroatom,yielding, for instance, an ether or alkylamine-containing linker.

The linker Z may optionally be substituted with one or moresubstituents, which may be the same or different, including hydrogen,halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl,heterocycloalkyl, heteroaryl, amine, hydroxy, oxo, formyl, acyl,carboxylic acid (—COOH), —C(O)R¹, —C(O)OR¹, carboxylate (—COO—), primaryamide (e.g., —CONH₂), secondary amide (e.g., —CONHR¹), —C(O)NR¹R²,—NR¹R², —NR¹S(O)₂R², —NR¹C(O)R², —S(O)₂R² , —SR¹, and —S(O)₂NR¹R²,sulfinyl group (e.g., —SOR₁), and sulfonyl group (e.g., —SOOR¹); whereinR¹ and R² may each independently be hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocycloalkyl and heteroaryl; wherein each of R¹and R² is optionally independently substituted with one or moresubstituents selected from the group consisting of halogen, hydroxyl,oxo, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionallysubstituted with one or more halogen or alkoxy or aryloxy, aryloptionally substituted with one or more halogen or alkoxy or alkyl ortrihaloalkyl, heterocycloalkyl optionally substituted with aryl orheteroaryl or oxo or alkyl optionally substituted with hydroxyl,cycloalkyl optionally substituted with hydroxyl, heteroaryl optionallysubstituted with one or more halogen or alkoxy or alkyl or trihaloalkyl,haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl and dialkylaminocarbonyl.

In certain preferred embodiments, the linker Z is a C₁₋₁₀ alkyl groupwhich may be unsubstituted or substituted one or more times by oxo,hydroxyl, carboxyl, amido or amino. Preferably, the linker Z is a C₁₋₄alkyl group. The alkyl group may be linear or branched. The alkyl groupmay also be interrupted one or more times by a heteroatom selected fromoxygen, sulfur and nitrogen. An example of such a di-carboxylic acidshaving a heteroatom interruption is thiodipropionic acid. In otherembodiments, the alkyl group may contain one or more double or triplebonds.

Group C is an ionic group ionically bonded to ionizable group A andcontains at least one thiol reactive selected from a Michael acceptor, asuccinimidyl-containing group, a maleimido-containing group, azlactone,a benzoxazinone derivative, vinyl sulfone, vinyl sulfoximine, vinylsulfonate, vinyl phosphonate, benzoxazinone, isocyanate, epoxide, anelectrophilic moiety containing a leaving group, an electrophilic thiolacceptor, acrylic or acrylate group, a methacrylic or methacrylategroup, a styrene group, an acryl amide group, a methacryl amide group, amaleate group, a fumarate group, an itaconate group, a vinyl ethergroup, an allyl ether group, an allyl ester group, a vinyl ester group,asulfonate group, a phosphonate group, a sulfoxide group, a sulfonamidegroup, a sulfinimide group, a sulfinamide group, a sulfonimidate group,or a sulfonimidamide group.

In some embodiments, the active agent of Formula II has one of thefollowing structures:

b. Excipients

The formulations typically contain one or more cosmetically acceptableexcipients. Cosmetically acceptable excipients include, but are notlimited to preservatives, antioxidants, chelating agents, sunscreenagents, vitamins, dyes, hair coloring agents, proteins, amino acids,natural extracts such as plant extracts, humectants, fragrances,perfumes, oils, emollients, lubricants, butters, penetrants, thickeners,viscosity modifiers, polymers, resins, hair fixatives, film formers,surfactants, detergents, emulsifiers, opacifying agents, volatiles,propellants, liquid vehicles, carriers, salts, pH adjusting agents (e.g., citric acid), neutralizing agents, buffers, hair conditioning agents,anti-static agents, anti-frizz agents, anti-dandruff agents, absorbents,and combinations thereof.

The formulations typically contain at least two cosmetically acceptableexcipients. In some forms, the formulations contain the active agent,water, and optionally a preservative and/or fragrance.

The formulation for treating hair may be in any suitable physical form.Suitable forms include, but are not limited to low to moderate viscosityliquids, lotions, milks, mousses, sprays, gels, creams, shampoos,conditioners, and the like. Suitable excipients, such as those listedabove, are included or excluded from the hair care formulation dependingon the form of use of the formulation (e.g., hair spray, cream,conditioner, or shampoo).

The pharmaceutical excipient is typically present in an amount rangingfrom about 10 wt % to about 99.99 wt % of the formulation, preferablyabout 40 wt % to about 99 wt %, more preferably from about 80 wt % toabout to about 99 wt %.

i. Surfactants

Surfactants are surface-active agents that are able to reduce thesurface tension of water and cause the hair formulation to slip acrossor onto the skin or hair. Surfactants also include detergents and soap.The surfactants may be amphoteric, anionic, or cationic. Suitablesurfactants that may be used in the formulation include, but are notlimited to, 3-aminopropane sulfonic acid, almond amide, almondamidopropyl betaine, almond amidopropylamine oxide, aluminumhydrogenated tallow glutamate, aluminum lanolate, aminoethyl sulfate,aminopropyl lauryl glutamine, ammonium C₁₂₋₁₅ alkyl sulfate, ammoniumC₁₂₋₁₅ pareth sulfate, ammonium C₁₂₋₁₆ alkyl sulfate, ammonium C₉₋₁₀perfluoroalkylsulfonate, ammonium capryleth sulfate, ammoniumcapryleth-3 sulfate, ammonium monoglyceride sulfate, ammonium sulfate,ammonium isothionate, ammonium cocoyl sarcosinate, ammonium cumenesulfonate, ammonium dimethicone copolyol sulfate, ammoniumdodecylbenzenesulfonate, ammonium isostearate, ammonium laureth sulfate,ammonium laureth-12 sulfate, ammonium laureth-5 sulfate, ammoniumlaureth-6 carboxylate, ammonium laureth-7 sulfate, ammonium laureth-8carboxylate, ammonium laureth-9 sulfate, ammonium lauroyl sarcosinate,ammonium lauryl sulfate, ammonium lauryl sulfosuccinate, ammonium myrethsulfate, ammonium myristyl sulfate, ammonium nonoxynol-30 sulfate,ammonium nonoxynol-4 sulfate, ammonium oleate, ammonium palm kernelsulfate, ammonium polyacrylate, ammonium stearate, ammonium tallate,ammonium xylene sulfonate, ammonium xylene sulfonate, amp-isostearoylgelatin/keratin amino acids/lysine hydroxypropyltrimonium chloride,amp-isostearoyl hydrolyzed collagen, apricot kernel oil PEG-6 esters,apricot amide, apricot amidopropyl betaine, arachideth-20, avocadamide,avocadamidopropyl betaine, babassuamide, babassuamidopropyl betaine,babassuamidopropylamine oxide, behenalkonium chloride, behenamide,behenamide, behenamidopropyl betaine, behenamine oxide, sodium laurethsulfate, sodium lauryl sulfate, a polyoxyether of lauryl alcohol orceteareth-20, or combinations thereof.

Suitable anionic surfactants include, but are not limited to, thosecontaining carboxylate, sulfonate and sulfate ions. Examples of anionicsurfactants include sodium, potassium, ammonium of long chain alkylsulfonates and alkyl aryl sulfonates such as sodium dodecylbenzenesulfonate; dialkyl sodium sulfosuccinates, such as sodium dodecylbenzenesulfonate; dialkyl sodium sulfosuccinates, such as sodiumbis-(2-ethylthioxyl)-sulfosuccinate; and alkyl sulfates such as sodiumlauryl sulfate. Cationic surfactants include, but are not limited to,quaternary ammonium compounds such as benzalkonium chloride,benzethonium chloride, cetrimonium bromide, stearyl dimethylbenzylammonium chloride, polyoxyethylene and coconut amine. Examples ofnonionic surfactants include ethylene glycol monostearate, propyleneglycol myristate, glyceryl monostearate, glyceryl stearate,polyglyceryl-4-oleate, sorbitan acylate, sucrose acylate, PEG-150laurate, PEG-400 monolaurate, polyoxyethylene monolaurate, polysorbates,polyoxyethylene octylphenylether, PEG-1000 cetyl ether, polyoxyethylenetridecyl ether, polypropylene glycol butyl ether, Poloxamer® 401,stearoyl monoisopropanolamide, and polyoxyethylene hydrogenated tallowamide. Examples of amphoteric surfactants include sodiumN-dodecyl-.beta.-alanine, sodium N-lauryl-β-iminodipropionate,myristoamphoacetate, lauryl betaine and lauryl sulfobetaine.

More than one surfactant may be included in the formulation.

The surfactants are optionally included in an amount ranging from about0.1% to about 15% by weight of the formulation, preferably about 1% toabout 10% by weight of the formulation.

ii. Emollients

Emollient refers to a material that protects against wetness orirritation, softens, soothes, coats, lubricates, moisturizes, protects,and/or cleanses the skin. Suitable emollients for use in theformulations include, but are not limited to, a silicone compound (e.g.,dimethicone, cyclomethicone, dimethicone copolyol or a mixture ofcyclopentasiloxane and dimethicone/vinyldimethicone cross polymer,cyclopentasiloxane polysilicone), polyols such as sorbitol, glycerin,propylene glycol, ethylene glycol, polyethylene glycol, caprylyl glycol,polypropylene glycol, 1,3-butane diol, hexylene glycol, isoprene glycol,xylitol; ethylhexyl palmitate; a triglyceride such as caprylic/caprictriglyceride and fatty acid ester such as cetearyl isononanoate or cetylpalmitate. In a specific embodiment, the emollient is dimethicone,amidodimethicone, dimethiconol, cyclopentasiloxane, potassiumdimethicone PEG-7 panthenyl phosphate, or combinations thereof. Morethan one emollient may be included in the formulation.

The emollient is optionally included in an amount ranging from about0.5% to about 15% by weight of the formulation, preferably from about 1%to about 10% by weight of the formulation.

iii. Emulsifiers

The formulation may also contain one or more emulsifiers. Suitableemulsifiers include, but are not limited to, copolymers of anunsaturated ester and styrene sulfonate monomer, cetearyl alcohol,glyceryl ester, polyoxyethylene glycol ether of cetearyl alcohol,stearic acid, polysorbate-20, ceteareth-20, lecithin, glycol stearate,polysorbate-60, polysorbate-80, or combinations thereof. More than oneemulsifier may be included in the formulation.

The emulsifier is optionally included in an amount ranging from about0.05%-15% by weight of the formulation, preferably from about 0.1%-10%by weight of the formulation.

iv. Preservatives

One or more preservatives may be included in the formulation. Suitablepreservatives include, but are not limited to, glycerin containingcompounds (e.g., glycerin or ethylhexylglycerin or phenoxyethanol),benzyl alcohol, parabens (methylparaben, ethylparaben, propylparaben,butylparaben, isobutylparaben, etc.), sodium benzoate,ethylenediamine-tetraacetic acid (EDTA), potassium sorbate, and/orgrapefruit seed extract, or combinations thereof. More than onepreservative may be included in the formulation. Other preservatives areknown in the cosmetics industries and include salicylic acid, DMDMHydantoin, Formaldahyde, Chlorphenism, Triclosan, Imidazolidinyl Urea,Diazolidinyl Urea, Sorbic Acid, Methylisothiazolinone, SodiumDehydroacetate, Dehydroacetic Acid, Quaternium-15, StearalkoniumChloride, Zinc Pyrithione, Sodium Metabisulfite, 2-Bromo-2-Nitropropane,Chlorhexidine Digluconate, Polyaminopropyl biguanide, BenzalkoniumChloride, Sodium Sulfite, Sodium Salicylate, Citric Acid, Neem Oil,Essential Oils (various), Lactic Acid, and Vitamin E (tocopherol).

The preservative is optionally included in an amount ranging from about0.1% to about 5% by weight of the formulation, preferably from about0.3% to about 3% by weight of the formulation. Preferably, theformulations are paraben free.

v. Conditioning Agents

One or more conditioning agents may be included in the formulation.Suitable conditioning agents include, but are not limited to,silicone-based agents (e.g., silicone quaternium-8), panthenol,hydrolyzed wheat and/or soy protein, amino acids (e.g. wheat aminoacids), rice bran wax, meadowfoam seed oil, mango seed oil, grape seedoil, jojoba seed oil, sweet almond oil, hydroxyethyl behenamidopropyldimonium chloride, aloe leaf extract, aloe barbadensis leaf juice,phytantriol, panthenol, retinyl palmitate, behentrimonium methosulfate,cyclopentasiloxane, quaternium-91, stearamidopropyl dimethylamine, andcombinations thereof.

The conditioning agent(s) is optionally included in an amount rangingfrom about 0.1% to about 5% by weight of the formulation, preferablyfrom about 0.3% to about 3% by weight of the formulation.

vi. Diluents

Diluent, as used herein, refers to a substance(s) that dilutes theactive agent. Water is the preferred diluent. The formulation typicallycontains greater than one percent (by wt) water, preferably greater thanfive percent (by wt) water, more preferably greater than 50% (by wt)water, and most preferably greater than 80% (by wt) water. Alcohols,such as ethyl alcohol and isopropyl alcohol, may be used at lowconcentrations (about 0.5% by weight of the formulation) to enhance hairpenetration and/or reduce odor.

vii. Viscosity Modifying Agents

The formulations may contain one or more viscosity modifying agents,such as viscosity increasing agents. Classes of such agents include, butare not limited to, viscous liquids, such as polyethylene glycol,semisythetic polymers, such as semisynthetic cellulose derivatives,synthetic polymers, such as carbomers, poloxamers, andpolyethyleneimines (e.g., PEI-10), naturally occurring polymers, such asacacia, tragacanth, alginates (e.g., sodium alginate), carrageenan,vegetable gums, such as xanthan gum, petroleum jelly, waxes, particulateassociate colloids, such as bentonite, colloidal silicon dioxide, andmicrocrystalline cellulose, surfactants, such as PPG-2 hydroxyethylcoco/isostearamide, emulsifiers, such as disteareth-75 IPDI, and salts,such as sodium chloride, and combinations thereof.

viii. Antioxidants

The formulation may contain one or more antioxidants. Examples include,but are not limited to, tocopheryls, BHT, ascorbic acid, camelliasinensis leaf extract, ascorbyl palmitate, magnesium ascorbyl phosphate,carotenoids, resveratrol, triethyl citrate, arbutin, kojic acid,tetrahexydecyl ascorbate, superoxide dismutase, zinc, sodiummetabisulfite, lycopene, ubiquinone, and combinations thereof.

ix. Opacifying Agents

The formulation may contain one or more opacifying agents. Opacifyingagents are added to the formulations to make it opaque. Suitableopacifying agents include, but are not limited to, glycol distearate andethoxylated fatty alcohols.

c. Forms of the Formulation

i. Sprays

The formulation may be in the form of a spray. The spray typicallyincludes the active agent and a cosmetically acceptable carrier. In someembodiments, the carrier is water or a water and alcohol mixture. Thespray formulation optionally includes an antioxidant, sunscreen agent,vitamin, protein, peptide, plant extract, humectant, oil, emollient,lubricant, thickener, hair conditioning agent, polymer, and/orsurfactant. Preferably, the spray formulation includes a preservative.In some embodiments, the formulation includes a fragrance. In someembodiments, the formulation includes a surfactant. In some embodiments,the formulation contains water, fragrance, a preservative, and an activeagent. In some embodiments, the formulation contains water, fragrance, apreservative, and an active agent. In some embodiments, the formulationcontains water, a preservative, fragrance, an active agent, and ananti-static agent. In some embodiments, the formulation contains water,a preservative, fragrance, an active agent, and a hair conditioningagent. In some embodiments, the formulation contains water, apreservative, fragrance, an active agent, and a surfactant.

The hair spray formulations may be dispensed from containers thatinclude aerosol dispensers or pump spray dispensers. Such dispensers areknown in the art and are commercially available from a variety ofmanufacturers.

Propellant

When the hair spray formulation is dispensed from a pressurized aerosolcontainer, a propellant may be used to force the formulation out of thecontainer. Suitable propellants include, but are not limited to, aliquefiable gas or a halogenated propellant. Examples of suitablepropellants include dimethyl ether and hydrocarbon propellants such aspropane, n-butane, iso-butane, CFCs, and CFC-replacement propellants.The propellants may be used singly or admixed.

The amount of propellant may range from about 10% to about 60% by weightof the formulation. The propellant may be separated from the hair repairformulation as in a two compartment container. Other suitable aerosoldispensers are those characterized by the propellant being compressedair, which can be filled into the dispenser using a pump or equivalentdevice prior to use. Conventional non-aerosol pump spray dispensers,i.e., atomizers, may also be used to apply the formulation to the hair.

ii. Conditioners

The formulation may be in the form of a conditioner. The conditionertypically includes the active agent in a suitable carrier. Additionally,the conditioner may include cationic polymers derived frompolysaccharides, for example cationic cellulose derivatives, cationicstarch derivatives, cationic guar derivatives and cationic locust beangum derivatives, synthetic cationic polymers, mixtures or combinationsof these agents. The formulation may comprise other synthetic or naturalpolymers or polymers derived from biological preparation processes,which are functionalized, where appropriate, for example with cationicor neutral groups. These polymers may have a stabilizing orstrengthening action on the formulation, and/or a conditioning action(deposition on the surface of the skin or the hair).

The active agent may be included in any suitable concentration. Typicalconcentrations of active agent in the conditioner range from smallamounts such as approximately 0.01% (by wt), preferably at least 0.1%(by wt), to large amounts, such as up to 50% (by wt). Preferably theconditioner contains the active agent in a concentration ranging from0.1% (by wt) to 5% (by wt), more preferably from 0.1% wt to 3% (by wt).While greater concentrations of active agent could be present in theconditioner, they are generally not needed to achieve the desiredresults.

iii. Shampoos

The hair repair formulation may be in the form of a shampoo. The shampootypically includes the active agent in a suitable carrier. The activeagent may be included in any suitable concentration. Typicalconcentrations of the active agent in the shampoo range from smallamounts such as approximately 0.01% (by wt), preferably at least 0.1%(by wt), to large amounts, such as up to 50% (by wt). Preferably theshampoo contains the active agent in a concentration ranging from 0.1%(by wt) to 5% (by wt), more preferably from 0.1% (by wt) to 3% (wt).While greater concentrations of active agent could be present in theshampoo, they are generally not needed to achieve the desired results.

Additionally, the shampoo may include from about 0.5% to about 20% byweight of a surfactant material. Surfactants utilized in shampoocompositions are well-known in the art and are disclosed, for example,in U.S. Pat. No. 6,706,258 to Gallagher et al. and U.S. Pat. No.7,598,213 to Geary et al.

iv. Creams, Lotions, Gels, and Polish

The hair, skin, or nail repair formulation may be in the form of acream, lotion, gel, or polish. The cream, lotion, gel, or polishtypically includes the active agent in a suitable carrier. The activeagent may be included in any suitable concentration. Typicalconcentrations of the active agent in the cream, lotion, gel, or polishrange from small amounts such as approximately 0.01% (by wt), preferablyat least 0.1% (by wt), to large amounts, such as up to 50% (by wt).Preferably the cream or lotion contains the active agent in aconcentration ranging from 0.1% (by wt) to 5% (by wt), more preferablyfrom 0.1% (by wt) to 3% (by wt). While greater concentrations of activeagent could be present in the cream or lotion, they are generally notneeded to achieve the desired results.

Additionally, the formulation, depending on use, may include an oil, ahair conditioning agent, and/or a thickening agent. The cream, lotion,gel, or polish may also include a fragrance, a plant extract, and/or asurfactant. The cream, lotion, gel, or polish may be packaged in a tube,tub, bottle, or other suitable container.

v. Liquid Active Agent Formulations

In some embodiments, a liquid active agent formulation is provided,which is mixed at the time of use with a second formulation, such as acoloring or highlighting formulation. In these embodiments, the liquidactive agent formulation may contain any suitable concentration ofactive agent in a suitable carrier, typically a diluent, such asdescribed above. The concentration of the active agent is suitable toprovide a mixture with the appropriate final volume and finalconcentration of active agent.

For example, a liquid active agent formulation can contain aconcentration of active agent ranging from about 5% (by wt) to about 50%(by wt) or greater. In a preferred embodiment, the liquid active agentformulation contains about 20% (by wt) active agent.

For highlighting applications, prior to use, a sufficient volume of aliquid active agent formulation is mixed with a sufficient volume of ahighlighting formulation to form a highlighting mixture having thedesired concentration of active agent. Typical concentrations of theactive agent in the highlighting mixture range from small amounts, suchas approximately at least 0.01% (by wt), preferably at least 0.1% (bywt), to large amounts, such as up to 50% (by wt). Preferably thehighlighting mixture contains the active agent in a concentrationranging from 0.1% (by wt) to 5% (by wt), more preferably from 0.1% (bywt) to 3% (wt). While greater concentrations of active agent could bepresent in the highlighting mixture, they are generally not needed toachieve the desired results.

. Methods of Use

A. Treatment of Hair with Coloring Agents

a. Apply the Coloring Formulation to the Hair

The coloring formulation is generally applied to an individual's hairfollowing normal hair coloring procedures that are known to thoseskilled in the art. Typically, hair color treatments include twocomplementary processes: applying a bleaching formulation to bleach thehair's natural pigment and/or other artificial pigments present in thehair, and diffusion of dye precursors into the hair, followed bycoupling reactions that result in the formation of chromophores withinthe hair shaft, which are too large to diffuse out of the hair. Thebleaching formulation typically contains a bleaching agent to lightenthe hair and produce free thiol groups. The hair coloring formulationmay be a highlighting formulation, such as formed by mixing bleachpowder and developer. More complex colors may contain several precursorsand many couplers, and may involve multiple reactions.

The dye precursors may contain several ingredients, each with differentfunctions. The first ingredient is usually an alkalizing agent (usuallyammonia and/or an ammonia substitute, such as monoethanolamine [MEA]).The alkalizing agent serves a number of roles in the hair colorantprocess including swelling the hair fiber to aid in diffusion of the dyeprecursors. The dye precursors generally include p-diamines andp-aminophenols. Precursors are oxidized to active intermediates oncethey have penetrated the hair shaft. Intermediates then react with colorcouplers to create wash resistant dyes. More specifically, theintermediates, in the presence of an oxidant, couple with anotheroxidation dye intermediate molecule to form a large fused ring colorcompound within the hair shaft. The precursor intermediate shouldpenetrate the hair shaft prior to the coupling reaction since the fusedring product is too large to penetrate the hair shaft. Couplers modifythe color produced by the oxidation of precursor compounds. The primarydifference between demi-permanent and permanent products is thealkalizing agent and the concentration of peroxide. The cuticle does notswell as greatly with demi-permanent dyes, making dye penetration lessefficient compared to permanent coloring products.

Several coloring formulations use a reducing agent, such as sodiumbisulfate, to break disulfide bonds in the hair, allowing deeperpenetration of the hair coloring dyes into the hair. Specifically, themethod includes reducing some of the disulfide linkages of the cystinein the hair shafts to thiol groups while breaking hydrogen bonds. Thereducing process changes the chemical and cosmetic characteristics ofthe hair, which are undesirable.

The hair dyeing process may be followed by a shampoo and conditioningtreatment, a neutralizing rinse or an acid balanced shampoo containingin addition to cationic or amphoteric surfactants, cation-activeemollients and quarternary polymers. Alternately, the hair dying processmay be followed by application of the active agent formulationsdescribed herein, before a shampoo and/or conditioning treatment.

b. Apply the Active Agent Formulation to the Hair

The active agent formulation may be applied simultaneously with the haircoloring formulation or subsequently to the application of the haircoloring formulation. For example, the active agent formulation may bemixed with the hair coloring treatment and the mixture, containing boththe active agent and the hair coloring treatment, may be applied to thehair.

Alternatively, subsequent to coloring the hair, the active agentformulation, or a formulation thereof is applied to the hair. Althoughthe active agent is typically applied on the same day as the coloringtreatment, it may be applied later such as within 1 to 2 weeks followingtreatment with the reducing agent. Typically, the amount of active agentformulation (or a mixture of the active agent formulation and the haircoloring formulation) applied is sufficient to saturate the hair. Theactive agent may be applied to the hair as a single application, orapplication of the active agent may be repeated one or more times.Typically, the amount of active agent formulation applied in eachapplication is sufficient to saturate the hair. The volume of activeagent formulation applied to the hair in each application may be about 1to about 100 mL per person depending on their length and volume of hair.In some embodiments, application of the active agent could be repeatedimmediately (e.g. within 10 to 15 seconds) or approximately 1, 5, 7.5,10, 12.5, 15, 17.5, or 20 minutes after the first application.

The active agent can be rinsed and shampooed from the hair immediatelyfollowing application, for example within 10, 15, 25, 30, 45, or 60seconds, or two, three, four, or five minutes after application.Alternatively, the active agent may be rinsed from the hair within about30 minutes following application, preferably between about 5 minutes andabout 20 minutes, more preferably about 10 minutes after application ofthe active agent to the hair, depending on hair type.

If the active agent formulation is combined with the hair coloringtreatment and applied as a mixture to the hair, then the mixture remainson the hair as long as needed for the hair coloring treatment. Typicallythe mixture is applied for approximately 10 minutes. The mixture isremoved from the hair in accordance with standard methods for haircoloring treatments, e.g., rinse and shampoo, approximately 10 minutesafter applying the mixture.

The active agent formulation is rinsed from the hair after itsapplication. The hair may be rinsed and subsequently washed immediately(e.g. within 10 to 15 seconds following application) after the finalapplication of the active agent. Preferably, the hair is rinsed and/orwashed about 10 minutes or later after the final application of theactive agent, such as about 15 minutes to about 30 minutes, optionallyabout 20 minutes after repeated application of the active agent to thehair.

The active agents are generally washed from the individual's hair on thesame day as they are applied. In contrast, traditional perms which useonly hydrogen peroxide (and do not involve the addition of the activeagent) are generally not washed for at least 48 hours followingapplication (washing the hair prior to 48 hours following a traditionalpermanent treatment may result in significant loss in the amount of curlin the hair and/or cause damage to the hair).

The formulation described herein improves hair quality, such asappearance (e.g., sheen) and feel, and decreases hair breakage when thehair is subjected to treatments, such as coloring or permanent waving.

In some embodiments, hair breakage decreases by 5, 10, 15, 20, 25, 30,35, 40, 45, or 50% or higher after treatment with the active agentcompared to untreated hair from the same individual. Hair breakage is asignificant problem encountered during coloring and other treatments.

B. Chemical Treatment of Hair with a Reducing Agent

In one embodiment, prior to treatment with the active agent, the hairhas been subjected to a reducing agent used for waving (also referred toherein as hair perming or permanent waves), and/or curling of the hair.

a. Apply a Reducing Agent to the Hair

The first step in waving or curling hair is breaking the cysteinedisulfide bonds to form free thiol moieties. The process for breakingthe cysteine disulfide bonds is via application of a reducing agent. Theprocess for applying the reducing agent involves following normalperming or hair straightening procedures that are known to those skilledin the art. For example, to perm hair, the hair is first washed and seton perm rods of various sizes. Second, a reducing agent, such asthioglycolate reducing solution or lotion is applied to the hair. Thehair is allowed to set for a specified period of time, and then thethioglycolate solution is rinsed from the hair.

The application of hydrogen peroxide in this process is optional. Insome processes, such as when treating previously chemically treatedhair, hydrogen peroxide is generally not used. In other processes, suchas when perming virgin hair, hydrogen peroxide may be added. In theseembodiments, hydrogen peroxide is typically added after the reducingagent is rinsed out. Then the hydrogen peroxide is rinsed from the hairprior to adding the active agent.

b. Apply the Active Agent

Subsequent to the reducing treatment, one or more of the active agent,or a formulation thereof is applied to the hair. Although the agent istypically applied on the same day as treatment with the reducing agent,it may be applied later such as within 1 to 2 weeks following treatmentwith the reducing agent.

Typically, the amount of active agent formulation applied is sufficientto saturate the hair. The agent is generally rinsed and shampooed fromthe hair after the desired level of hair waving or curling is achieved.In some embodiments, the active agent is rinsed from the hairimmediately (e.g. within 10, 15, 25, 30, 45, or 60 seconds followingapplication) following the final application of the active agent.Alternatively the hair may be rinsed and washed about within about 30minutes following application, preferably between about 5 minutes andabout 20 minutes, more preferably about 10 minutes after the finalapplication of the active agent to the hair, depending on the hair type.The active agent can be rinsed from the hair within 10, 15, 25, 30, 45,60 seconds from the hair after application, and still achieve a desiredlevel of hair waving or curling.

The active agent may be applied to the hair as a single application, orapplication of the agent may be repeated one or more times. Typically,the amount of active agent formulation applied in each application issufficient to saturate the hair. In some embodiments, the volume ofactive agent formulation applied to the hair in each application isabout 1 to about 10 mL per perm rod. In some embodiments, application ofthe active agent could be repeated immediately (e.g. within 10 to 15seconds) or approximately 1, 5, 7.5, 10, 12.5, 15, 17.5, or 20 minutesafter the first application. In some embodiments, the second applicationis about 7 minutes to about 10 minutes after the first application.

The active agent is rinsed from the hair after its application. The hairmay be rinsed and washed immediately (e.g. within 10 to 15 secondsfollowing application) after final application of the active agent.Alternatively the hair may be rinsed and washed about 10 minutes orlater after the final application of the active agent, such as about 15minutes to about 30 minutes, preferably about 20 minutes after repeatedapplication of the active agent to the hair.

The active agents are generally washed from the individual's hair on thesame day as they are applied. In contrast, traditional perms which useonly hydrogen peroxide (and do not involve the addition of the activeagent) are generally not washed for at least 48 hours followingapplication (washing the hair prior to 48 hours following a traditionalpermanent treatment may result in significant loss in the amount of curlin the hair and/or cause damage to the hair).

The formulations described herein can be applied to hair to improve hairquality, such as appearance (e.g., sheen) and feel, and decrease hairbreakage when the hair is subjected to subsequent treatments, such ascoloring.

In some embodiments, hair breakage decreases by 5, 10, 15, 20, 25, 30,35, 40, 45, or 50% or higher after application of the active agentcompared to untreated hair from the same individual. Hair breakage is asignificant problem encountered during coloring and other treatments.

C. Treatment of Skin or Nails with the Active Agent

In one embodiment, a formulation containing one or more of the activeagents is applied to the skin or nails. Application of the active agentformulation to skin or nails can help repair damaged disulfide bonds dueto natural wear and tear or natural aging.

In some embodiments the active agent formulation is in the form of acream or lotion, which is suitable for application to the skin or nails.In other embodiments, the active agent formulation is in the form of agel or polish, which is suitable for application to the nails.Typically, the amount of active agent formulation applied is sufficientto treat the damaged keratin in the skin or nails. The active agentformulation may be applied to the skin or nails in a single application,or application of the formulation may be repeated one or more times, asneeded, to achieve the desired effect of repairing keratin damage and/orstrengthening the skin or nails.

IV. Kit

Kits for treating hair are provided. In one embodiment, the kittypically contains a first formulation for coloring hair. The haircoloring formulations typically include a reducing agent capable ofreducing disulfide bonds in hair to produce free thiol groups. The kitalso includes a second formulation containing an effective amount of theactive agent.

The kit may further include a developer bottle, gloves, shampoo,conditioner, and/or an odor eliminator. Instructions for use of the kitare also typically provided.

Typically the kit contains more than one container (or more than onecompartment in a given container) to ensure that the lightening agent(e.g., peroxides) or the coloring agent is stored separately from theactive agent.

A. First Formulation

The first formulation in the kit can be a coloring treatment. The firstformulation may be formulated as two or more components which may bemixed together before application to the hair. For example, the firstformulation may be in the form of two components such as a dye precursorand an oxidant. Typically, the hair coloring formulation contains areducing agent capable of reducing the disulfide bonds in hair andproducing reduced free thiol groups. Suitable reducing agents include,but are not limited to, thioglycolic acid, thiolactic acid,dihydrolipoate, thioglycerol, mercaptopropionic acid, sodium bisulfite,ammonium bisulfide, zinc formaldehyde sulfoxylate, sodium formaldehydesulfoxylate, sodium metabisulfite, potassium borohydride, pegylatedthiols and hydroquinone. The amount of the reducing agent in the firstformulation is sufficient to rupture a sufficient number of disulfidebonds for effective diffusion of the hair coloring ingredients as wouldbe appreciated by one of skill in the art.

The components of the first formulation may differ depending on the haircoloring treatment desired (such as for semi-permanent, demi-permanent,or permanent hair color), the texture of the hair, the sensitivity ofthe user's skin, and such the like. Hair coloring formulations fordifferent hair coloring treatment, hair texture, and hair sensitivityare known to those of skill in the art.

B. Active Agent Formulation

The second formulation contains one or more active agents in aneffective amount. Suitable formulations containing the active agents arediscussed above. The second formulation may be in any suitable form.Suitable forms include, but are not limited to, low to moderateviscosity liquids, lotions, milks, mousses, sprays, gels, creams,shampoos, conditioners, and the like. The second formulation will bepresent in a suitable container, which depends on the form of theformulation.

In one embodiment, the active agent formulation is provided as two ormore separate ingredients. For example, the active agent may be providedas a dry powder in a sealed package and the excipient provided in a vialor other container. A suitable mixing container for the active agent andthe excipient may be provided.

In some embodiments, the active agent formulation (or secondformulation) is mixed with the first formulation (or hair coloringtreatment), and the mixture is applied to the hair.

C. Other Materials in the Kit

The kit optionally contains shampoos and conditioners. Suitable shampoosand conditioners include, but are not limited to LiQWd® HydratingShampoo and LiQWd® Hydrating Conditioner.

The kit may further contain an odor eliminator. The odor eliminator canbe incorporated into the first or second formulation, or a mixturethereof. Alternately, the odor eliminator is present in a suitablecontainer for use before or after washing the second formulation fromthe hair. Some suitable odor eliminators are known to those of ordinaryskill in the art.

It is understood that the disclosed method and formulations are notlimited to the particular methodology, protocols, and reagents describedas these may vary. It is also to be understood that the terminology usedherein is for the purpose of describing particular embodiments only, andis not intended to limit the scope of the present invention which willbe limited only by the appended claims.

EXAMPLES Example 1 Color Retention and Texture of Colored Hair Treatedwith the Active Agent Formulation

General

Three hair samples were obtained from a human subject and cut in ½ inchwide wefts.

Coloring formulation: The permanent hair coloring formulation wasobtained from a L'Oreal® permanent hair coloring service (L’Oreal®Majirel permanent color #10 with 20 volume peroxide).

Active agent formulation: Maleic acid, at a concentration of 200 mg in10 g total solution (water) was used.

Methods

The hair samples were washed with a clarifying shampoo then towel dried.The samples were then colored with the L'Oreal® permanent hair colorservice, which was left on the hair samples for approximately 35-40minutes.

The first color treated hair sample (“control”) was subsequently rinsedand washed with Liqwd® Hydrating Shampoo and Conditioner five timesbefore being photographed.

The active agent formulation was applied to the second and third colortreated hair samples via a spray bottle and massaging using the fingers.The active agent formulation was left on the second hair sample for aperiod of about 1 minute and on the third sample for a period of about10 minutes. The hair samples were subsequently rinsed, and then washedwith Liqwd® Hydrating Shampoo and Conditioner five times before beingexamined.

Results:

The hair samples treated with the active agent formulation showed bettercolor retention, more shine, and less frizz than the control. The hairsamples treated with the active agent formulation felt smoother to thetouch and combined with the lower frizz and added sheen gave an overallhealthier appearance over the control.

Example 2 Comparison of Color Retention in Traditionally Permed Hair andHair Permed Using the Active Agent Formulations

Method

A ½ inch wide weft of hair sample, obtained from a human subject, waswashed with clarifying shampoo then towel dried. Ammonium thioglycolateor dithiothreitol was mechanically pulled through the hair with a wideand a fine toothcomb several times then left on the hair for 10 minutesto 1 hour. The hair was then rinsed for 30 seconds to 1 minute withwater, and then towel dried.

The active agent formulation, described in Example 1 (Maleic acid inwater), was then applied via a needle nose applicator drenching the hairand leaving it on for 7.5 minutes. This step was repeated, for a totalof 15 minutes. The hair was then rinsed for 1-2 minutes, shampooed, andthen conditioned with various salon shampoo and conditioner brands,including LiQWd® Hydrating Shampoo and Hydrating Conditioner.

A second sample of hair was straightened, as described above, but usinghydrogen peroxide instead of the active agent formulation. The hairsamples were washed and conditioned repeatedly.

Comparison of Hair Color:

After both hair samples were washed five times using LiQWd® HydratingShampoo and LiQWd® Hydrating Conditioner, the samples were examined fortheir color retention.

Results

The hair sample treated with the active agent formulation displayed acolor closer in intensity to the hair sample prior to the first washing,compared to the hair treated with hydrogen peroxide.

Example 3 Comparison of Hair Treated with Highlighting FormulationApplied Simultaneously with Active Agent Formulation and Hair Treatedwith Highlighting Formulation Alone

The active agent formulation in Example 1 contained maleic acid atconcentrations of 2.0 g in 10 g total solution (water).

Two swatches of human hair were tested. A sample was taken from the samehead, 1 inch wide, and split in half. The color was medium brown and hadbeen previously color treated with an unknown professional hair color.

Swatch 1, ½ inch wide and 8 inches long, was lightened with traditionalhighlighting ingredients mixed with the active agent formulation. 1 ozof Joico Verocolor Veroxide developer-20 volume was mixed with 1 ozJoico Verolight powder bleach to form the highlighting formulation. Then9mL of the active agent formulation was added to the highlightingformulation to form a mixture.

The mixture was applied on the Swatch 1 hair with an applicator brush asthe hair lay on aluminum foil. The foil was then wrapped around theswatch and allowed to process for 35 minutes. The swatch was rinsed andshampooed one time.

Swatch 2, the control, ½ inch wide and 8 inches long, was lightened withtraditional highlighting ingredients in the absence of the active agentformulation. 1 oz of Joico Verocolor Veroxide developer-20 volume wasmixed with 1 oz Joico Verolight powder bleach to form a highlightingformulation with a creamy consistency.

The highlighting formulation was applied on the Swatch 2 hair with anapplicator brush as the hair lay on aluminum foil. The foil was thenwrapped around the swatch and allowed to process for 35 minutes. Theswatch was rinsed and shampooed one time.

Results

A noticeable difference in hair quality between Swatch 1 and Swatch 2was observed. Swatch 1 hair was softer, less frizzy, appeared hydrated,with more shine than the control, Swatch 2.

Both swatches were washed and conditioned 5 more times with the samenoticeable benefits of Swatch 1(treated with the mixture of highlightingformulation and active agent formulation) compared to the control,Swatch 2 (treated with highlighting formulation, alone).

Example 4 Comparison of Hair Treated with Bleaching Formulation AppliedSimultaneously with Active Agent Formulation and Hair Treated withBleaching Formulation Alone

General

Two hair samples were obtained from a human subject and cut in ½ inchwide wefts.

Methods

(1) 0.5 ounces of powder lightener (Clairol Professional, Basic White)and 0.5 ounces of conditioning cream developer (Redken, Blonde Icing)were combined to form a bleaching mixture. 3.5 g of2-(methacryloyloxy)ethan-1-aminium (Z)-3-carboxyacrylate (12 wt % inwater) was added to the bleaching mixture and thoroughly mixed with abrush.

(2) The bleaching mixture prepared was brushed onto the swatches of hairwith a brush in order to thoroughly coat the strands of hair. Themixture coated hair was wrapped in aluminum paper and allowed to standunder ambient conditions for a period of two hours.

(3) After the two hour bleaching period the swatches of hair were washedwith shampoo and the hair was subsequently allowed to air dry.

Results

A noticeable difference in hair quality between Swatch 1 and Swatch 2was observed. Swatch 1 hair was demonstrated no discernible breakage,great feel, and a healthy appearance while the control (treated withbleaching formulation, alone) showed some breakage, had a rough feel,and was frayed with an unhealthy appearance.

Example 5 Comparison of Hair Treated with Bleaching Formulation AppliedSimultaneously with Active Agent Formulation and Hair Treated withBleaching Formulation Alone

General

Two hair samples were obtained from a human subject and cut in ½ inchwide wefts.

Methods

(1) 0.5 ounces of powder lightener (Clairol Professional, Basic White)and 0.5 ounces of conditioning cream developer (Redken, Blonde Icing)were combined to form a bleaching mixture. 3.5 g of prop-2-en-l-aminium(Z)-3-carboxyacrylate (10 wt % in water) was added to the bleachingmixture and thoroughly mixed with a brush.

(2) The bleaching mixture prepared was brushed onto the swatches of hairwith a brush in order to thoroughly coat the strands of hair. Themixture coated hair was wrapped in aluminum paper and allowed to standunder ambient conditions for a period of two hours.

(3) After the two hour bleaching period the swatches of hair were washedwith shampoo and the hair was subsequently allowed to air dry.

Results

A noticeable difference in hair quality between Swatch 1 and Swatch 2was observed. Swatch 1 hair was demonstrated no discernible breakage,great feel, and a healthy appearance while the control (treated withbleaching formulation, alone) showed some breakage, had a rough feel,and was frayed with an unhealthy appearance.

Example 6 Comparison of Traditional Perm Versus Perm Using Maleic Acid

General

Hair samples were obtained from a human subject and cut in ½ inch widewefts.

Reducing agents: Ammonium thioglycolate (ATG) was obtained from apermanent wave kit manufactured by Zotos. 300 mg of Dithiothreitol in a10 g solution was also used as the reducing agent.

Active agent formulation: Maleic acid at a concentration of 200 mg in 10g total solution (water) was used.

Methods

Method for perming hair using the active agent

The hair was washed with clarifying shampoo, towel dried, and thenrolled around a perm rod. Ammonium thioglycolate or dithiothreitol wasthen applied to the hair and left on the hair for 10 minutes to 1 hour.The hair was then rinsed for 30 seconds to 1 minute and then blotted drywith a towel.

The active agent formulation was applied to the hair, via a needle noseapplicator, drenching the hair. The active agent formulation was left onthe hair for a period of about 7.5 minutes. The hair was drenched for asecond time with the active agent formulation and left for a second 7.5minutes, for a total of 15 minutes. The hair was then rinsed with waterfor about 1-2 minutes then unrolled from the perm rods. After the hairwas removed from the perm rods, the hair was shampooed and conditionedwith various salon shampoo and conditioner brands, including LiQWd®Hydrating Shampoo and Hydrating Conditioner. The washing and dryingsteps were repeated 40 times.

A second portion of hair was permed as described above, except, hydrogenperoxide was used instead of the active agent formulation.

Results

Both perms (utilizing the active agent formulation or hydrogen peroxide)showed only slight reduction in the overall curl after 40 cycles ofwashing and drying with the same shampoo and conditioner. However, theappearance and texture of the perm using the active agent formulationshowed more sheen and less frizz compared to the perm using hydrogenperoxide.

Example 7 Comparison of Hair Breakage Due to Repeated Application ofTraditional Perm and the Active Agent Formulation

Methods

Two hair samples were obtained. Both samples were treated withdithiothreitol or ammonium thioglycolate as described in Example 4. Oneof the hair samples was subsequently treated with the active agentformulation (Maleic acid in water), while the other was neutralized withhydrogen peroxide. The process was completed the same day for the hairtreated with the active agent formulation. The process was completed inthree days with hydrogen peroxide (traditional perm).

The procedure was repeated three times for each hair sample over a 48hour time period.

Results

Upon visual inspections, the second hair sample treated with the activeagent formulation showed little or no signs of breakage. However, thefirst hair sample treated with hydrogen peroxide showed significantbreakage.

Example 8 Comparison of the Extent of Damage to Hair Previously Relaxedwith a Japanese Relaxer

Methods

Two samples of hair, the first previously straightened with a Japaneserelaxer (Yuko), and the second previously straightened with a no lyerelaxer (African Pride Miracle Deep Conditioning) were obtained. Thesamples were treated as described in Examples 4 and 5 using the activeagent formulation (Maleic acid in water).

Another hair sample, previously straightened with a no lye relaxer(African Pride Miracle Deep Conditioning) was obtained. The sample wastreated with a traditional hair straightening perm (Zotos).

Results

The hair samples treated with the active agent formulation showed nonoticeable damage. However, the sample treated with a traditional permshowed significant breaking, even during application.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of skill in the artto which the disclosed invention belongs. Publications cited herein andthe materials for which they are cited are specifically incorporated byreference.

Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, many equivalents to the specificembodiments of the invention described herein. Such equivalents areintended to be encompassed by the following claims.

1-29. (canceled)
 30. A method for bleaching hair comprising: (a)combining developer with maleic acid or salts thereof and bleach powderto form a bleaching mixture having an alkaline pH; (b) applying thebleaching mixture to the hair.
 31. The method of claim 30, wherein themaleic acid or salts thereof in step (a) is in an amount ranging from0.1 wt % to 5 wt % of the bleaching mixture.
 32. The method of claim 30,wherein the maleic acid or salts thereof in step (a) is in an amountranging from 0.1 wt % to 3 wt % of the bleaching mixture.
 33. The methodof claim 30, wherein the bleach powder comprises potassium persulfateand ammonium persulfate.
 34. The method of claim 30, further comprising:(c) rinsing or shampooing the hair, or a combination thereof, whereinstep (c) occurs subsequent to step (b).
 35. The method of claim 30,wherein following step (b), the hair is lighter compared to the hairprior to step (b).
 36. The method of claim 30, wherein the bleachingmixture does not comprise an oxidative dye precursor.